Influenza viruses differ in recognition of 4-O-acetyl substitution of sialic acid receptor determinant.

Equine alpha 2-macroglobulin (EM), known to contain both Neu5Ac and Neu4,5Ac2 sialic acid residues, was treated with Vibrio cholerae sialidase for the selective removal of Neu5Ac and was compared with the untreated EM for its binding by a panel of influenza viruses. Type A H3N2 virus strains having Leu in position 226 of their hemagglutinin (HA) changed the affinity for sialidase-treated EM only slightly, if at all, indicative of their ability to bind the 4-O-Ac-substituted Neu5Ac receptor determinant. At the same time, all B and H1N1 viruses, some H2N2 variants, as well as H3N2 strains with 226 Gln studied were unable to recognize Neu4,5Ac2 moieties of EM. Molecular modeling based on the known 3-D structure of H3 HA complexed with sialyllactose (Weis et al. (1988) Nature 333, 426-431) predicts that the 4-O-Ac substituent of sialic acid would protrude with its carbonyl oxygen inside the receptor-binding site of HA, thus possibly interfering with binding.

[Use of highly purified subvirion trivalent flue vaccine ("Grippovak") in groups with a high risk of complications]. / Primenenie glubokoochishchennoi subvirionnoi trekhvalentnoi grippoznoi vaktsiny ("Grippovak") v gruppakh vysokogo riska oslozhnenii.

During the epidemic season of 1989-1990 the subunit vaccine Grippovac was used in 20 asylums for old people and psychoneurological invalids in Moscow for the protection of the inhabitants and the personnel from influenza. Follow-up of the vaccinees during the period from November 1989 to March 1990 revealed that the use of this vaccine decreased the incidence of influenza-like diseases (ILD) 3.4-4.1 times among the vaccinees in comparison with that in the nonvaccinated control groups and significantly decreased the severity of the course of ILD, as well as the mortality because of ILD, among those vaccinees who had contacted ILD. This is indicative of good prospects of regular vaccinal prophylaxis of influenza at asylums for old people and other persons at a high risk of influenza complications.

[Live enteroviral vaccines for the emergency nonspecific prevention of mass respiratory diseases during fall-winter epidemics of influenza and acute respiratory diseases]. / Zhivye énterovirusnye vaktsiny dlia ékstrennoi nespetsificheskoi profilaktiki massovykh respiratornykh zabolevanii vo vremia osenne-zimnikh épidemii grippa i ostrykh respiratornykh zabolevanii.

The results of the 3-year controlled trials of a new method of nonspecific urgent prophylaxis of influenza and acute respiratory diseases (ADR) by immunization of healthy adults with standard live enterovirus oral vaccines, introduced in 2-3 administrations at intervals of 7-10 days, at the initial stages of autumn and winter epidemics are presented. Observations, carried out in three republics, covered more than 150,000 persons immunized with enterovirus interferonogenic vaccines. A considerable decrease in morbidity rate among the vaccinees was achieved (on the average, by 3.2 times) in comparison to that among nonimmunized subjects. The method of nonspecific prophylaxis with live enterovirus interferonogenic vaccines is recommended during outbreaks of diseases induced simultaneously by several causative agents of influenza and ARD, as well as by pathogenic enterovirus strains.

Recognition by human A and B influenza viruses of 8- and 7-carbon analogues of sialic acid modified in the polyhydroxyl side chain.

To evaluate the recognition by influenza viruses of the C9-C7 polyhydroxylated moiety of sialic acid (SA) receptor determinant a novel assay has been developed based on the assessment of binding by the solid-phase immobilized virus of the enzyme-labeled sialyglycoprotein fetuin treated by periodate or periodate/borohydride to contain an 8-carbon aldehyde, 7-carbon aldehyde, or corresponding hydroxyl analogues of SA. Some features of recognition by human influenza viruses of these SA analogues were type and subtype specific, especially marked differences being found between type A and type B viruses. At the same time a significant diversity was observed among virus strains belonging to the same subtype. The assay described provides a new tool for the differentiation of influenza viruses according to receptor binding properties and for an investigation of molecular interactions in the receptor binding site of the virus.

Heterogeneity of influenza B virus strains isolated in a local area of the disease during an influenza outbreak.

Ten strains of influenza B virus isolated in a local focus during an influenza outbreak were found to include 9 virus strain variants as demonstrated by different antigenicity of their haemagglutinin, ts-marker, sensitivity to heating at 56 degrees C/30 min, and to non-specific serum inhibitors. These strains induced antibodies in rats which interacted more actively with the virus isolated in earlier periods of this outbreak than with that isolated later. It might indicate that all strains originated from the same parent strain of virus, which induced the influenza outbreak in this area.

[Monoclonal antibodies against tick-borne encephalitis virus glycoprotein: preliminary characterization]. / Monoklonal'nye antitela k glikoproteidu virusa kleshchevogo éntsefalita: predvaritel'naia kharakteristika.

Characterization of 12 clones of monoclonal antibodies (MAb) generated for the main immunogen of tick-borne encephalitis virus, glycoprotein E, is presented. The following MAb parameters have been determined: constants of binding with antigen, classes and subclasses of immunoglobulins, the activity in two variants of solid-phase enzyme-immunoassay, binding with protein A, and MAb behavior in serologic tests: hemagglutination-inhibition, diffuse precipitation in agar, and virus neutralization. The preliminary studies revealed the presence in these MAb of at least three groups of antibody complementary to various nonoverlapping sites on the structural virus glycoprotein. Further employment of these MAb in practical and research work is discussed.

Olivopontocerebellar atrophy in a large Iakut kinship in eastern Siberia.

One-hundred cases of olivopontocerebellar atrophy, type 1, were found and studied in the Iakut population of Eastern Siberia. The disease followed a slowly progressive course of cerebellar insufficiency caused by degeneration in the cerebellar cortex, nuclei pontis, and inferior oliva. The disorder shows an autosomal dominant pattern of inheritance with a lower penetrance in females. The disease spread from a small region in the Aldan valley 200 to 300 years ago.

[Antigenic characteristics of influenza B virus strains isolated in an orphanage during an influenza outbreak in Moscow in the winter of 1988]. / Antigennaia kharakteristika shtammov virusa gripa B, izolirovannykh v detskom dome-internate pri vspyshke grippa v Moskve zimoi 1998 g.

Examinations of ARD patients in an orphanage for defective children in Moscow during an influenza outbreak in the winter of 1988 yielded 12 influenza virus strains, including 6 influenza B strains and 6 influenza A (H3N2) strains. The antigenic analysis of hemagglutinin of influenza B virus isolates showed that with respect to the B/Leningrad/179/86 strain (an antigenic analogue of B/Ann Arbor/1/86 strain recommended for inclusion into the influenza vaccine for 1987-1988) they could be divided into 2 groups: antigenically close to the B/Leningrad/86 strain (isolate B/712) and markedly differing from it (the remaining isolates). As compared with reference strains of the previous years, all the new virus isolates fell into 4 groups: isolate B/712 antigenically related to B/Hong Kong/73 and B/Leningrad/86 strains; B/722 antigenically close to B/Singapore/222/79 and B/USSR/100/83 strains; B/724, an antigenic analogue to B/USSR/100/83; and the remaining isolates, to some or other extent, differing from various reference strains. This attests to simultaneous circulation of various antigenic variants of influenza B virus during the 1988 winter outbreak of influenza in Moscow. An interesting feature of the B/712/88 isolate consists in its antigenic specificity of hemagglutinin being indistinguishable from that of B/Hong Kong/8/73 strains.

[Use of monoclonal antibodies for differentiating strains of the virus causing the hemorrhagic fever with renal syndrome]. / Primenenie monoklonal'nykh antitel dlia differentsiatsii shtammov virusa gemorragicheskoi likhoradki s pochechnym sindromom.

Using monoclonal antibody and animal immune sera the experiment confirmed the existence of antigenic relationships between the strains of virus of hemorrhagic fever with renal syndrome (HFRS) isolated in the USSR from Clethrionomys glareolus and members of all known serotypes of HFRS virus. Clear-cut differentiation was made from serotypes Apodemus and Rattus, and cross-relationships were shown between the strains isolated in the USSR and Prospect Hill virus (PHV), a member of the serotype Microtus isolated in the USA.

[Results of coded trials of the activity of the trivalent subunit influenza vaccine Grippovak in Moscow kindergartens in December 1983 through the 1st quarter of 1984]. / Rezul'taty zashifrovannykh ispytanii aktivnosti trekhvalentnoi sub''edinichnoi grippoznoi vaktsiny Grippovak v detskikh sadakh Moskvy v dekabre 1983 g.--I kvartale 1984 g.

During the autumn-winter epidemic of influenza-like diseases in December, 1983--first quarter, 1984, in Moscow commissioned coded observations on the effectiveness of prophylactic vaccination against influenza of 3-7-year-old children with a preparation "Grippovak SE-AZh" were carried out in day-care centers. In the previous large-scale trials, 1981-1984, the "Grippovak" had been evaluated positively as a completely harmless, serologically and immunologically active preparation reducing 3-3.5-fold the number of laboratory-verified cases of viral type A and B influenza in the vaccinees. In 1986, however, the "Journal of Microbiology, Epidemiology, Immunology" (JMEI, 2: 49-54) published a paper whose authors, on behalf of the Commission which had checked the preparation in the day-care centers (Z.A. Bashliaeva, A.A. Sumarokov, et al.), came to a conclusion that "Grippovak" was ineffective in children. Other members of the above Commission disagreeing with this conclusion made a repeat analysis of the decoded materials of the observations in the day-care centers using computer methods and demonstrated that because of significant prevalence of non-influenza ARD cases and recurrent (up to 44%) ARD cases in children in the 4 months of observation, it was impossible to judge the effectiveness of the vaccine by comparison of the total incidence of influenza and ARD from the clinical data alone in the vaccinees and controls.(ABSTRACT TRUNCATED AT 250 WORDS)

[Immunogenicity and the protective effectiveness of the subunit trivalent influenza vaccine Grippovac]. / Immunogennost' i protektivnaia éffektivnost' sub"edinichnoi grippoznoi trekhvalentnoi vaktsiny "Grippovak".

In the process of the immunological approbation of several experimental batches of the triyalent subunit influenza vaccine Grippovac, the pronounced immunogenicity of the antigens of all strains contained in the vaccine was established; most of the vaccinees were found to retain sufficiently high antibody titers for a year, and the essential total increase of antibody titers was found to occur after a single booster immunization. The serological checking of the diagnosed cases of influenza among immunized and nonimmunized children, carried out in two boarding schools during the influenza epidemic in the winter of 1984-1985 provided the proofs of the high effectiveness of Grippovac in preventing viral influenza, types A and B: the decrease of influenza morbidity among the immunized children reached 79,5-67,2-66,5% and the total morbidity rate in influenza in these two boarding scholls dropped, on the average, 3,0-3,5 times.

[Isolation of the influenza B virus in MDCK cells]. / Vydelenie virusa grippa B v kletkakh MDCK.

The frequency of influenza B virus isolation from clinical specimens is much higher when a continuous line of dog kidney cells, MDCK, is employed, and not the developing chick embryos. Among 9 influenza B virus strains isolated during the influenza epidemic of 1983-1984 winter, 8 strains were isolated in MDCK cells and only 1 in chick embryos. The influenza B virus isolates were similar to influenza B/Singapore/222/79 virus differing from it in HI titres 2-16-fold.

Subunit influenza virus vaccine Grippovac SE-AZh (vaccination of adults).

Grippovac SE-AZh a polytype, subunit influenza virus vaccine containing H1N1 and H3N2 influenza A virus strains and one influenza B virus strain has been tested in 80 volunteers. The trials demonstrated the harmlessness, the absence of adverse reactions, and except of the B type, the high antigenicity of vaccine preparation when administered in two injections. The optimal dose of each viral strain haemagglutinin (HA) was 15 micrograms in 0.5 ml.

[Characteristics of the glycoproteins of vaccinal strains of the influenza viruses solubilized by octyl-beta-D-glucopyranoside]. / Kharakteristika glikoproteidov vaktsinnykh shtammov virusov grippa, soliubilizirovannykh oktil-beta-D-gliukoprianozidom.

The use of a nonionic detergent, octyl-beta-d-glucopyranoside (OG), under optimal conditions is highly effective in selective solubilization of membrane proteins (glycoproteins) of influenza A and B viruses, including the strains currently recommended for polytype inactivated influenza vaccines. The yield of hemagglutinin was 84-90% of the initial level in the virion concentrate. The antigenic stability of hemagglutinin of the A/H3 subtype upon storage for over 2 years and the A/H1 subtype for about 1 year (the observation period) was demonstrated. According to the results of electron microscopic studies, the glycoproteins solubilized with OG are present before removal of the detergent in the form of isolated subunits, "rosettes", and their agglomerates, and after removal of the detergent in the form of virosomes (clumps of subunits on liposomes) more heterogeneous in size (20 to 130 nm) and shape than the intact virus. The process of virosome formation is reversible and depends on the presence of the detergent. The resulting glycoproteins of influenza virus vaccine strains solubilized with the OG detergent possess the characteristics which make this agent promising for use in the manufacture of polytype subunit vaccine.